Sustained release pharmaceutical dosage unit forms are well-known, and carboxyvinylpolymer and polyvinylpyrrolidone are substituents known to be used in a variety of sustained release pharmaceutical dosage unit forms.
U.S. Pat. No. 3,458,622 issued to Hill on July 29, 1969, discloses controlled release tablets which are produced by blending a medicament with polyvinylpyrrolidone and carboxyvinylpolymer, granulating, drying, and compressing into tablets. The ratio of polyvinylpyrrolidone:carboxyvinylpolymer in these controlled release tablets is from about 1:10 to 10:1. Hill discloses that "(w)hen the resulting tablet is placed in water or gastric fluid, the two polymeric substances react to form a complex of low solubility which is gumlike in consistency and . . . retards the diffusion of the active material from the tablet." Hill also notes that there is a rapid release of some of the medicament because " . . . the active material near the surface is allowed to diffuse out of the tablet fairly rapidly. As the moisture penetration becomes deeper, the restraining matrix becomes thicker and reduces the diffusion rate of the active substance. When the tablet is transferred to intestinal fluid, . . . the entire matrix is then eroded," thus providing the sustained release of the active substance trapped therein. (See column 1, lines 38-52.)
U.S. Pat. No. 3,634,584 issued to Poole on Jan. 11, 1972, discloses a controlled release tablet in which the controlled release is achieved by combining carboxyvinylpolymer and polyethyleneglycol. Poole achieves a combination of rapid release and sustained release by producing a two-layer tablet, one layer containing the controlled release formulation and the other layer containing a formulation of the active material which disintegrates rapidly to make the active material contained therein quickly available.
El Egakey, M. A., "In vitro and in vivo Release Studies of Nitrofurantoin from Coated Crystals", Acta Pharmaceutica Technologica, Vol. 28, No. 4 (1982), pp. 267-271, discloses pharmaceutical dosage forms in which crystals of nitrofurantoin were coated with a mixture of polyvinylpyrrolidone and carboxyvinylpolymer. Sustained release of this dosage form is achieved by having different coated crystal particles release their entrapped nitrofurantoin at different times. The coated crystal particles can be made into a capsule dosage form by filling them into a hard gelatin capsule shell, or can be made into a tablet by compressing them together in a standard tableting operation.
U.S. Pat. Nos. 4,343,789 and 4,404,183 issued to Kawata, Aruga, Ohmura, Sonobe, Yoneya & Sone on Aug. 10, 1982 and Sept. 12, 1983, respectively, disclose sustained release dosage forms made by dissolving an active material with a polymeric material and then drying the solution to form an amorphous mixture of the active material and polymer. The amorphous material is broken into small particles which are then filled into hard gelatin capsule shells. Either carboxyvinylpolymer or polyvinylpyrrolidone are disclosed as polymeric materials which can be used to produce these sustained release capsules.
U.S. Pat. No. 4,126,672 issued to Sheth & Tossounian on Nov. 21, 1978, discloses sustained release pharmaceutical capsules which are powder mixtures of medicaments with a hydrocolloid or mixture of hydrocolloids. Carboxyvinylpolymer is disclosed as one of the hydrocolloids useful in achieving such sustained release capsules. Sheth & Tossounian discloses that "(u)pon oral ingestion of the sustained release capsules . . . , the capsule shell dissolves leaving the formulation in contact with gastric fluid. Upon contact with gastric fluid, the outermost hydrophyllic colloid hydrates to form an outside barrier which substantially retains the shape of the capsule and therefore acts to prevent the mass from disintegrating." (See column 2, lines 38-44.) These hydrated powder masses swell in gastric fluid such that "they have a bulk density . . . less than one and therefore are buoyant in gastric fluid and thus are retained in a buoyant state in the stomach until substantially all the medicament is released therefrom." (See column 2, lines 10-14.) "(A)fter substantially all the medicaments therein are released, the gelatinous mass disperses." (See column 2, lines 35-37.)